A series of psychoactive drugs utilized to alleviate or exacerbate the symptoms of various mental disorders are known to interact with dopaminergic systems in the brain. These observations have led to the notion that dysfunction of the dopamine systems in brain may be involved in the manifestation and expression of mental disorders. A number of these diseases may result in part from genetic and/or developmental defects of the brain. Since it is likely that fetuses are exposed to drugs capable of interacting with these central dopaminergic systems during critical periods in their organization and development, it is proposed to investigate the response of embryonic and fetal brains to drugs affecting various aspects of dopaminergic function including synthesis, storage and release as well as interaction with membrane receptors. Experiments are described utilizing in situ preparations which will 1) define the embryonic sites of origin of the mature dopaminergic system, and 2) the effects on their subsequent development after expposure to drugs known to interact with the mature system. Parallel experiments with simpler systems composed of reorganizing cellular aggregates in the presence and absence of psychoactive drugs will 1) allow an examination of the pharmacological mechanisms by which the drugs modify CNS development and 2) elucidate the normal neurochemical mechanisms by which the embryonic nervous system properly organizes itself. The results should 1) enable a definition of the possible effects of embryonic exposure to these drugs on the subsequent development of normal brain function, 2) generate new animal models of brain dysfunction related to mental disease, and 3) shed new insight into the possibel mechanisms by which defined neurochemical systems organize themselves in the brain during early development.